Asthma is a chronic inflammatory disease that effects approximately 17 million Americans. Despite the availability of inhaled beta-adrenoceptor (betaAR) agonists and corticosteroids, 1.8 million emergency room visits a year occur due to severe asthma attacks demonstrating a significant unmet medical need. The Company intends to develop and commercialize INV102, a therapeutic targeting beta-adrenoceptors that greatly reduces asthma bronchoconstriction when administered prophylactically. The Company has data in which chronic administration of the small molecule INV102 to asthmatic mice causes up-regulation of beta2-adrenoceptors. Surprisingly, these mice do not exhibit severe bronchoconstriction in response to a spasmogen. Our research mirrors independent research in which over-expression of beta2-adrenoceptors in airway smooth muscle in transgenic mice also greatly reduces airway hyper-reactivity - the hallmark of asthma. Since these preliminary studies have only been performed in a murine model of allergic asthma, follow-on studies will be performed in a rat asthma model to determine if the response is generalizable to all animals and ultimately to humans. Additionally, as INV102 is a beta inverse agonist, it binds directly to (2- adrenoceptors and can worsen airway constriction if administered at high levels. Consequently, the specific aims are: 1) to identify a safe, low level starting dose of INV102 that does not result in airway constriction in a rat asthma model and 2) develop a dose escalation scheme that maximally alleviates bronchoconstriction in this rat model. The long-term objectives of the proposed project are to provide both preclinical animal data (Phase I grant) to support an IND followed by human clinical data (Phase II grant) demonstrating the safety and efficacy of this drug to ameliorate the severe exacerbations of asthma to support FDA approval.